Could Managing Cholesterol Prevent Alzheimer’s?

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Posted on Nov 25, 2018, 7 p.m.

A handful of gene variants have been found to increase some people’s risk of dementia and cardiovascular disease in the largest genetic study of Alzheimer’s disease to date, which implies that we may be able to repurpose some cardiovascular drugs to treat and/or prevent AD, as published in the journal Acta Neuropathologica.

Worldwide scientists are working hard to track down the root causes of Alzheimer’s disease to move towards a cure for this devastating disease. It is known that this is a neurodegenerative condition that has a strong genetic component, such as a patient with one copy of APOE4 gene variant being twice as likely to develop AD, while having 2 copies may increase the risk by up to 12 fold.

APOE genes encode apolipoprotein E proteins, in combination with fats or lipid this protein forms lipoprotein molecules, which play roles in transportation of cholesterol and other types of fat through the bloodstream; meaning there is an establish link between cholesterol and AD. New research has uncovered many other genes that connect risk of AD with risk of cardiovascular disease.

Large genome wide association studies and validation tools were used to examine DNA from over 1.5 million people, specifically examining for differences in DNA between those with risk factors for heart disease such as high BMI, type 2 diabetes, and high triglyceride and cholesterol levels.

Analysis found 90 points in the genome called single nucleotide polymorphisms that had an associated risk for cardiovascular disease and Alzheimer’s disease. Across a total of 19 chromosomes 90 SNPS were identified. 6 of these strongly influenced AD risk and increased levels of blood lipids; findings which confirmed results of previous studies.

Some of the SNPs were in genes not previously associated with the risk of Alzheimer’s disease, including several SNPs in the CELF1/MTCH2/SP11 region on chromosome 11 that previous studies had linked to immunity.

Findings were replicated in a large genetic study of healthy individuals, finding participants with a family history of AD were more likely to have the newly identified risk genes even if the had no symptoms.

Genes that influenced lipid metabolism were the same ones that were related to risk of AD. Genes that contributed to other cardiovascular risk factors such as BMI index and type 2 diabetes didn’t seem to contribute to genetic risk for Alzheimer’s disease.

This study presents opportunity to consider repurposing drugs targeting pathways involved in lipid metabolism to investigate whether some of these drugs may be useful in delaying and/or preventing Alzheimer’s disease.

Keeping cholesterol and triglyceride levels in check may help to manage risk of AD in some people, however more research is needed to confirm this. Findings imply irrespective of what causes what, CVD and AD pathology co-occur because they are linked genetically; if one carries this handful of gene variants they could be at risk for both cardiovascular disease and Alzheimer’s disease.

With so much to learn about how genes driving AD also increase risks for other health problems, it’s time to start thinking about these risks more holistically explains Celeste M. Karch, Ph.D.